A rat homolog of the Drosophila enhancer of split (groucho) locus lacking WD-40 repeats.

In Drosophila, neurogenic loci function in defining cellular fate by interpreting the identity of other cells in the immediate environment. To begin studies of mammalian homologs of these genes, we have isolated two rat homologs of the neurogenic locus Enhancer of split. The protein encoded by the Drosophila Enhancer of split locus is complex and contains five distinct regions based on amino acid composition. One region contains six WD-40 repeats, which were first described in the beta subunit of the heterotrimeric guanine nucleotide-binding protein. One of the rat cDNAs we isolated, R-esp1, encodes a novel form that lacks the WD-40 repeating units. Data are presented demonstrating that the R-esp1 cDNA is a full-length clone encoding an expressed 24-kDa protein. Antibodies raised against this protein stain the nucleus of both PC-12 and GH3 cells. The second clone, R-esp2, encodes a full-length homolog containing WD-40 repeats. The hydrodynamic properties of in vitro translated R-esp1 and R-esp2 proteins indicate that they do not stably self-associate or form heterodimers. A model is presented for the possible role of the R-esp1 protein in the negative regulation of Enhancer of split proteins containing WD-40 repeats.